An FDA committee began a meeting yesterday that continues today to consider permitting new assisted reproduction-based technology that could address mitochondrial disorders, a serious human health problem. The technology also raises complex health issues of its own and invokes ethical questions.

The goal of the FDA meeting is articulated this way: “the committee will discuss oocyte modification in assisted reproduction for the prevention of transmission of mitochondrial disease or treatment of infertility.”

The technology, given the informal moniker of “3-parent” reproduction by some, in principle could in theory be very positive by preventing mitochondrial disorders in children. At the same time, as the “3-parent” name implies, this technology is controversial. It would be a complete departure from normal human reproduction and children produced using this approach would indeed have 3 biological parents.

Why would the kids have 3 parents?

The technology combines distinct materials from the human eggs of two women: one providing the nucleus or chromosomes depending on the approach and the other providing the rest of the oocyte that contains mitochondrial DNA. The hybrid egg is then fertilized with sperm of the father-to-be by IVF.

My stem cell colleague Shoukhrat Mitalipov of OHSU in Portland has been the pioneer in this area. A Washington Post article says:

The procedure was pioneered by Shoukhrat Mitalipov, a researcher at Oregon Health and Science University who focuses on early embryo development and stem cell biology. He has been able to produce five healthy monkeys using this technique and has proposed testing it in humans.

The hope given by this approach is that the mother providing the nuclear DNA, who also has faulty mitochondrial DNA, could nonetheless give birth to a healthy child via the healthy mitochondrial DNA of the donor. That goal is completely worthy.

However, like so many things in biotechnology, it is not that simple.

There are serious potential risks with this technology and these risks constitute my first reason for opposing FDA green-lighting of this technology.

What are the risks?

The 3-parent technique could produce children with serious and even fatal developmental disorders. In fact one of the reasons the FDA originally put a stop to this kind of technology in the first place was concern over it potentially causing chromosomal abnormalities. Although the method has worked in other species to produce seemingly normal offspring and similar techniques have even worked a few times in the distant past with actual humans when IVF doctors frankly didn’t have very many rules, there are reasonable concerns including some raised by scientists that this could be very risky for humans.

My second concern is more complicated, but can be articulated more simply with a question: is humanity wise enough to tinker with its own genome in ways that are heritable?

My answer is “no”. Do I need to provide examples of how unwise human beings can be?

Notably, the FDA will not consider bioethical or society concerns about the technology during its meeting.

My third concern is that this technology, if approved, will be expanded for elective procedures such as to treat age-related infertility and in that way be used to produce thousands of at-risk babies and significantly change the collective human genome permanently.

Others are more positive about the notion of moving this technology forward with humans.

The Post piece quotes some scientists including Susan Solomon, head of the NYSCF: “I don’t think we should be motivated by fear of the unknown….we are trying to stop a horrible, horrible disease”.

Evan Y. Snyder, Chair of the FDA committee, was quoted by The Post this way:

“There’s overall great concern for the well-being of these kids,” Evan Y. Snyder, the panel’s chairman, said at the meeting, summarizing some of the thoughts of the members. “I think there was a sense of the committee that at this particular point in time, there was probably not enough data either in animals or in vitro to conclusively move on to human trials . . . without answering a few additional questions.”

However, he also called the technology “incredibly intriguing” so it is apparent he can see the points raised on both sides. I think that’s good.

There is room to see both sides on this issue and each has logical points to be respectfully discussed.

It is unfortunate that some scientists are criticizing opponents of 3-parent technology as luddites.

For example Marcy Darnovsky, executive director of the Center for Genetics and Society wrote quite a reasonable opinion piece in the NY Times yesterday opposing the technology and was criticized on Twitter for it.

I thought she articulated her opinion quite well. Sure, you may disagree with her and I don’t agree with her 100%, but she has some good points that she articulated well and this was after all an opinion piece.

All of these kinds of issues need to be aired and debated. The FDA meeting is a great form for this discussion, although again it leaves off the ethical and societal issues. Ultimately I hope the FDA says “no” to the technology. Humanity just isn’t ready and the risks are too great.

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7 Comments

I believe that you titled this post wrong. You wrote “3 parent reproduction”, but I think that you were actually referring to “in vitro fertilization”?

40 years ago, IVF was an untested technology with grave safety concerns. And, those concerns were legitimized… IVF produces an incredible number of aneuploid embryos. Moreover, IVF has been used to treat age-related infertility, vastly changing the human genome. So, you want the FDA to ban IVF, right?

Is there any problem other than 50% of the zygotes having abnormalities? I’d say it’s worth finding out how the other 50% will progress — go from there.

Let’s be a little bit flexible while things are figured out.

In the big scheme of things, I don’t see that this planet really needs more humans. But such technologies will probably lead to an overall increase in the cost of reproduction — and a smaller total number of babies. Good for the planet. I wonder what the Pope would think…

I do not understand why people try to emphasize this gene therapy is going to cause parental rights issues. I think there are lots of exaggeration on the problems that this therapy may cause. We know that mitochondrial genome only contributes less than 0.1% of entire human genome and clearly there is no room to argue that the mitochondrial donor should have parental right. Besides, the potential problems with chromosomal defects are based on assumptions and there is no evidence that this new technique will present such threat; whereas, there is evidence from animal studies and in vitro human cell studies that there is no chromosomal defects in the fetus or the offspring. Should we just reject a new therapy that will help millions of people around the world based on suspicions and doubts? I say NO!
The fair thing to do would be to allow those people to have their share of say in this decision making who have kids with mitochondrial disease and potential mothers with mtDNA defects who would like to have healthy children.

I disagree with ‘ethical’ objections to permitting scientific experiments. Mainly because throughout human history technological advancements are capitalized upon for both good and evil simultaneously. Furthermore, it always seems that scientists who expouse all of their ‘ethical’ objections to other peoples research are mainly sucking up to the politcally run funding bodies run by idiotic deists like Paul Broun. I hate to be a dick about it, but it’s getting old.

Paul,
The mitochondrial replacement changes the pattern of inheritance, but not the genome itself (the DNA sequence). The mitochondrial genome is not modified, the nuclear genome is not modified. And you will probably agree that the techniques used for the mitochondrial replacement cannot achieve such a modification. Rather, it is the type of change occurring in human reproduction, that involves the combination of different nuclear genomes with different mitochondrial genomes. The oocyte changes its inheritable genotype with every fertilization event. It is conceptually wrong and misleading to link this to GMO, even if the point is made eloquent.

Thanks for the comment, Dieter.
We have a difference of opinion on this. Standard reproduction, mom (person A) and dad (person B) have a child, who has nuclear genome consisting of A and B and a mitochondrial genome A. In the proposed technology from the same parents, but with an infertile or subfertile mother, the child would have a nuclear genome consisting of A and B and a mitochondrial genome from a third-party woman let’s call C. Unless either (A) you don’t count the mitochondrial DNA as a genome or (B) you don’t count the entire swapping out of one mitochondrial genome for another, then child ABC has indeed been artificially given a modified genome. Logical?